The likelihood of venous thrombosis in individual patients can be only roughly estimated on the basis of clinical factors. Theoretically, global laboratory tests that detect hypercoagulability would be helpful in predicting thrombosis in the same way that routine tests for hypocoagulability (eg., PT, aPTT) are in predicting bleeding. In an attempt to produce such a global assay we have developed a "whole blood thrombin generation" assay. Clotting of fresh whole blood is stimulated by adding calcium and tissue factor. Subsamples of the clotting blood are assayed for thrombin activity. The measured parameters are the maximal concentration of thrombin activity, the time to peak activity, and the integral of thrombin activity x time. We have tested the effect of hematocrit, white cell count, and platelet count on these parameters and have found that all of the cell types influence thrombin generation. We have also found that the concentration of each coagulation factor and natural inhibitor also affects thrombin generation in the assay system. The test is now being applied in a group of patients with advanced malignancies who undergo major surgery. So far 8 patients have been studied. There are obvious changes in thrombin generation between the pre-operative and post-operative days. We have also begun to use this assay in assessing hypercoagulability in patients with sickle cell disease and plan to test it in patients with brain cancer, who also have a very high rate of venous thrombosis, to determine whether the results will be predictive of clinical events.